Donepezil and the alpha-7 agonist PHA 568487, but not risperidone, ameliorate spatial memory deficits in a subchronic MK-801 mouse model of cognitive impairment in schizophrenia.

Abstract

Cognitive impairment associated with schizophrenia (CIAS) is an important etiological feature of this disorder with implications for symptom severity and quality of life. Acute N-methyl-d-aspartate receptor (NMDAR) blockade using MK-801, a non-competitive antagonist to NMDARs, is assumed to produce temporary cognitive impairments in mice similar to those seen in schizophrenia patients. Less is known, however, about the effects of subchronic MK-801 administration on cognition. In the current study, twenty-eight male C57/BL6 mice received a daily dose of MK-801 (0.1mg/kg, i.p.) for seven days. Spatial memory was assessed using an object location task prior to MK-801 administration as well as at multiple time points after the treatment. Subchronic treatment with MK-801 caused lasting memory deficits, which were ameliorated by acute doses of an acetylcholinesterase inhibitor (donepezil) and an alpha-7 nicotinic agonist (PHA 568487), but were unaffected by acute administration of the atypical antipsychotic risperidone. Subchronic administration of MK-801 may lend this pharmaceutical model increased face validity, while its resemblance to prodromal schizophrenia makes it suitable for screening new CIAS treatments.

• Authors: Stoyo Karamihalev, Jos Prickaerts, Nick P van Goethem
• Journal: Behavioural brain research (Behav Brain Res) Vol. 272 Pg. 248-51 (Oct 01 2014) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 25036424 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antipsychotic Agents
• Aza Compounds
• Cholinesterase Inhibitors
• Dioxins
• Indans
• Nicotinic Agonists
• Nootropic Agents
• PHA-568487E
• Piperidines
• alpha7 Nicotinic Acetylcholine Receptor
• Dizocilpine Maleate
• Donepezil
• Acetylcholinesterase
• Risperidone

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antipsychotic Agents (pharmacology)
• Aza Compounds (pharmacology)
• Cholinesterase Inhibitors (pharmacology)
• Cognition Disorders (drug therapy, etiology, physiopathology)
• Dioxins (pharmacology)
• Disease Models, Animal
• Dizocilpine Maleate
• Donepezil
• Indans (pharmacology)
• Male
• Mice, Inbred C57BL
• Nicotinic Agonists (pharmacology)
• Nootropic Agents (pharmacology)
• Piperidines (pharmacology)
• Risperidone (pharmacology)
• Schizophrenia (complications, physiopathology)
• Schizophrenic Psychology
• Spatial Memory (drug effects)
• alpha7 Nicotinic Acetylcholine Receptor (agonists, metabolism)